1,1-disubstituted ethylene monomers and compositions containing the same are well known and, for the most part, widely available. They have utility in a broad array of end-use applications, most notably those which take advantage of their cure or polymerizable properties. Specifically, they find broad utility in coatings, sealants and adhesives, among other applications. Those 1,1-disubstituted ethylenes having one or, preferably, two electron withdrawing substituents at the 1 position have been used to provide adhesives and sealants with rapid cure rates and high bond strengths. Most notable among these are the cyanoacrylates such as ethyl cyanoacrylate and butyl cyanoacrylate. Another class of 1,1-disubstituted ethylenes that have demonstrated a lot of promise, but have limited, if any, commercial success are the methylidene malonates, including diethyl methylidene malonate.
Commercial success of the 1,1-disubstituted ethylenes is reliant upon a number of variables and factors including reasonable cost, high purity, good, especially long, shelf life and rapid cure rate. In an effort to achieve these goals, much work has been done to develop new and/or improved processes and synthetic schemes for their manufacture, purification and isolation.
For example, α-cyano acrylates have been prepared (U.S. Pat. No. 6,245,933) by reacting a cyanoacetate such as ethyl cyanoacetate with formaldehyde or a formaldehyde synthon such as paraformaldehyde in a Knoevenagel condensation followed by transesterification. The product mixture is then cracked and distilled to produce the α-cyano acrylate monomer.
Similarly, extensive efforts have been undertaken over many decades in an effort to produce, on a commercially viable basis, methylidene malonates. Two of the earliest methods for the production of dialkyl methylidene malonates, the simplest of the methylidene malonates, were the iodide method in which methylene iodide was reacted with dialkyl malonates and the formaldehyde method in which formaldehyde was reacted with dialkyl malonates in the presence of a base, in solution in alcohol solvents. As an alternative, Bachman et al. (U.S. Pat. No. 2,313,501) taught the reaction of a C1-C5 dialkyl malonate with formaldehyde in the presence of an alkali metal salt of a carboxylic acid, in solution in a substantially anhydrous carboxylic acid solvent, followed by fractional distillation to separate the desired product. D'Alelio (U.S. Pat. No. 2,330,033), on the other hand, alleged that such processes were erratic and more often produced yields that averaged 10 to 12 percent. D'Alelio espoused an improved process with yields on the order of 30% and higher by reacting a malonic acid ester with formaldehyde in a ratio of one mole of the former to at least one mole of the latter under alkaline conditions and, in most cases, in the presence of a polymerization inhibitor such as copper, copper acetate, hydroquinone, resorcinol, or catechol, to form a methylol derivative. The methylol derivative was then acidified to a pH below 7.0 using a suitable organic or inorganic acid in order to retard further reaction. The acidified mass is then dehydrated to form the corresponding methylidene malonate which is subsequently separated by distillation.
Not satisfied, Coover et al. (U.S. Pat. Nos. 3,221,745 and 3,523,097) took yet another approach to the formation of the methylidene malonates, electing to begin with a preformed dialkyl alkoxymethylenemalonate. In accordance with their process, the olefinic double bond of the latter compound was subjected to hydrogenation in the presence of a hydrogenation catalyst and the hydrogenated compound was then subject to pyrolysis in the presence of a phosphorous pentoxide inhibitor to strip off the alcohol to produce the methylene malonate. The resultant mass was then subjected to vacuum distillation at low temperature to separate an allegedly high purity methylidene malonate, though with a low yield. According to Coover et al., the use of low temperature distillation is said to prevent the contamination of the monomer with pyrolytic products that commonly result from high temperature distillation. These high purity monomers are said to be especially important for surgical applications.
Eventually, such efforts led to multi-step processes in which certain unsaturated molecules served as a platform for the formation of intermediate adducts from which the methylidene malonates were subsequently stripped and recovered. For example, Hawkins et al. (U.S. Pat. No. 4,049,698) found that certain malonic diesters could be reacted with formaldehyde and a linear, conjugated diene in the presence of a primary, secondary or tertiary amine at about reflux temperature to form an intermediate adduct that could then be readily pyrolyzed at temperatures in excess of 600° C. to split off the desired methylidene malonate. Similarly, Ponticello (U.S. Pat. No. 4,056,543) and Ponticello et al. (U.S. Pat. No. 4,160,864) developed processes by which asymmetrical methylene malonates, especially methyl allyl methylene malonate, were prepared from previously formed norbornene adducts, the latter having been prepared by the Diels-Alder reaction of an alkyl acrylate with cyclopentadiene at room temperature or with heating or use of a Lewis catalyst. The so formed monoester norbornene adducts were then reacted with an electrophile material in the presence of an alkyl-substituted lithium amide complex to form the diester adduct and subsequently pyrolyzed at a temperature of 400° C. to 800° C. at a pressure of 1 mm to 760 mm Hg in an inert atmosphere to strip off the desired methylene malonates.
Citing numerous disadvantages of the foregoing processes, which disadvantages were said to make them difficult, if not impossible, to adapt to industrial scale, Bru-Magniez et al. (U.S. Pat. Nos. 4,932,584 and 5,142,098) developed a process whereby anthracene adducts were prepared by reacting mono- or di-malonic acid ester with formaldehyde in the presence of anthracene, most preferably in a non-aqueous solvent medium in the presence of select catalysts. According to Bru-Magniez et al., the anthracene adducts were said to be readily produced in high yields with the desired methylidene malonates obtained by stripping them from the anthracene adduct by any of the known methods including heat treatment, thermolysis, pyrolysis or hydrolysis; preferably heat treatment in the presence of maleic anhydride.
Despite all of these efforts, issues remained and commercial success wanting owing to continued process frustrations, instability and unpredictability. Malofsky et al. (WO 2010/129068) solved some of the problems associated with process instability of the Retro-Diels-Alder adduct process by using polymerization inhibitors concurrent with or prior to stripping the adduct. Inhibitors such as trifluoroacetic acid and hydroquinone were used. In some examples, trifluoroacetic acid was also added to the distillate. Only limited curing studies were done, but the resultant malonates were able to be polymerized with tetrabutylammonium fluoride. Malofsky teaches a variety of purification processes including double distillation and extracting the product with an alkane such as n-heptane. Although this is an improvement over the art, these various purification processes can be costly and can reduce yield.
More recently, in an effort to find alternate and better routes to producing 1,1-disubstituted ethylenes, a focus has been directed to certain iminium based processes wherein select iminium salts are reacted with various compounds containing a methylene linkage having attached thereto at least one electron withdrawing group selected from nitriles, carboxylic acids, carboxylic esters, sulphonic acids, ketones or nitro to form electron deficient olefins. For example, McArdle et al. (WO 2008/050313, U.S. Pat. App. Pub. 2009/0203934, and U.S. Pat. No. 8,022,251) have taught the use certain specific iminium salts having a tertiary carbon atom attached to a nitrogen atom in the production of electron deficient olefins, most especially cyanoacrylates, however, methylidene malonates are also mentioned. The preferred process involved employing the select iminium salts in producing the 2-cyanoacrylates from nitriles such as ethyl cyanoacetate or malonitrile. When a formaldehyde derivative is used, the McArdle iminium salt can have the structure I:
wherein R3 is H, alkenyl, or alkynyl; R4 is a hydrocarbon moiety comprising a tertiary carbon which is attached to the N atom, where the tertiary carbon atom is attached to or a part of one or more substituents selected from linear, branched, or cyclic alkyl or alkenyl, or one or more together form a cyclic structure; and X is an anion such as a non-nucleophilic and/or an acidic anion. These imines may be formed by reacting formaldehyde or a source thereof with a primary amine having a tertiary carbon atom attached to the nitrogen to form an imine which is subsequently reacted with an acid under specified conditions to yield an iminium salt. Variations and refinements of the iminium process are taught in McArdle et al. (U.S. Pat. Nos. 7,659,423 and 7,973,119 and U.S. Pat. App. Pub. Nos. 2010/0210788 and 2010/0199888) and Bigi et al. (U.S. Pat. No. 7,718,821); the contents of all of which are hereby incorporated herein by reference.
The McArdle et. al. and Bigi et. al. iminium processes are not without their shortcomings. Both require high temperature reactions, temperatures which can promote the in-situ polymerization of the monomer product. Additionally, these processes require specific amines to form the iminium salts: amines that are oftentimes expensive and whose reaction byproducts are found, particularly in the case of methylidene malonates, to promote unwanted reactions in-situ, including, specifically dimerization of the monomer. Further, these processes must be conducted at a very low pH in order to prevent the retro-conversion of the iminium salt back to the imine by loss of a proton. From the perspective of the formation of cyanoacrylate monomers, these factors are of low concern, if any, as traditional processes for the production of cyanoacrylates involves the formation of the polymer which is then cracked, typically at high temperature, to form the monomer and have other issues that they too must content with. However, from the perspective of the formation of methylidene malonates, these factors are of considerable concern, particularly inasmuch as the yields and purity of the methylidene malonates so produced, as shown by McArdle et. al., are still low.
Thus, despite the advances that have been made, there are still improvements to be made. More importantly, there still remains a need for a commercially viable process for the production and isolation of methylidene malonates: a process which balances simplicity of process with common or at least less costly materials with high yields and purity and with consistency and repeatability.